Despite the availability of a variety of highly effective antibiotics, the search for new antibiotics is a continuing one. The primary reason for the continuing search is the reoccuring development of microorganisms which are resistant to existing antibiotic therapy. Thus there is a continuing need for new antibiotics which are either intrinsically more active than existing drug entities and thus can be administered in lower dosages to minimize the side effects of these powerful drugs, or are effective against resistant strains.
A number of aminoglycoside antibiotics are known, such as the gentamicin and kanamycin family of antibiotics. More recently, a new family of aminoglycosides, the fortimicins have been identified. See, for example, U.S. Pat. Nos. 3,976,768 and 3,931,400 which disclose Fortimicin A and B.
Although the fortimicin family is a relatively new group of antibiotics, clinical experience has shown that aminoglycoside antibiotics are susceptible to the resistant strain problem. In many cases, the resistance is R-factor mediated and is attributed to the ability of the bacteria to enzymatically modify the amino or hydroxy groups of the aminoglycoside antibiotics. Thus, there is a continuing need for new derivatives which are either more active then the currently known fortimicins, or which can be used against bacteria which have become or will become resistant to the known antibiotics. The present invention provides such derivatives.
Fortimicin E is coproduced with Fortimicin A and B by the fermentation of a microorganism belonging to the genus Micromonospora. Structurally, Fortimicin E is the C.sub.3, C.sub.4 epimer of Fortimicin B and thus can so be named as 3-epi,4-epifortimicin B. The 4-N-acyl derivatives of Fortimicin B are disclosed and claimed in our concurrently filed and co-assigned U.S. Patent application Ser. No. 863,012, filed Dec. 21, 1977.